MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

of the 2-aminoindane group which is related to

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

and produces similar subjective effects. It acts as a selective serotonin and norepinephrine releasing agent (SNRA). The drug shows greatly reduced serotonergic neurotoxicity in comparison to

in animals, although it still shows weak capacity for neurotoxicity with chronic use or in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

with

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

. MDAI was developed in the 1990s by a team led by David E. Nichols at

Purdue University Purdue University is a Public university#United States, public Land-grant university, land-grant research university in West Lafayette, Indiana, United States, and the flagship campus of the Purdue University system. The university was founded ...

. It has been encountered as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

and has been used recreationally with reported

street name A street name is an identifying name given to a street or road. In toponymic terminology, names of streets and roads are referred to as odonyms or hodonyms (from Ancient Greek 'road', and 'name', i.e., the Doric Greek, Doric and Aeolic Gre ...

s such as "sparkle" and "mindy". In addition to its recreational use, there has been interest in MDAI for potential use in

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

, for instance in drug-assisted psychotherapy.

Uses

Scientific research

MDAI and other similar drugs have been widely used in scientific research, as they are able to replicate many of the effects of MDMA, but without causing the serotonergic neurotoxicity associated with MDMA and certain related drugs. No tests have been performed on cardiovascular toxicity.

Recreational drug

MDAI has been advertised as a

. It started to be sold online from around 2007, but reached peak popularity between about 2010 to 2012, after bans on

mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug belonging to the amphetamine and cathinone classes. It is commonly referred to by slang names such as drone, , white magic, meow meow, and bubble. Chemically, it is similar to ...

came into effect in various countries. Many internet-sourced products claimed to be MDAI have been shown to contain

or other

substituted cathinone Substituted cathinones, or simply cathinones, which include some stimulants and Empathogen-entactogen, entactogens, are chemical derivative, derivatives of cathinone. They feature a substituted phenethylamine, phenethylamine core with an alkyl ...

derivatives, while generally containing no MDAI. The number of internet searches for MDAI has been considerably higher in the United Kingdom compared to Germany and the United States. MDAI is only non-neurotoxic in isolation but may become neurotoxic when mixed with other drugs. Three deaths were linked to MDAI use in the UK during 2011–2012, all involving symptoms consistent with

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

. Two of these also involved other drugs while one death appeared to be from MDAI alone.

Pharmacology

Pharmacodynamics

MDAI acts as a selective and well-balanced serotonin and norepinephrine releasing agent (SNRA) with much less (~10-fold lower) effect on dopamine release. In addition to inducing the release of the

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

s, MDAI also inhibits their reuptake. For comparison to MDAI, MDA and

are well-balanced releasing agents of serotonin, norepinephrine, and dopamine (SNDRAs). Conversely, the profile of monoamine release with MDAI is very similar to that of (''R'')-MDMA (''levo''-MDMA), which like MDAI is also a well-balanced SNRA with about 10-fold reduced impact on dopamine release, though MDAI is several-fold more potent than (''R'')-MDMA ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

''. In contrast to MDMA, MDAI shows no

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for any of the

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s (K_i = all >10μM). This notably includes the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor, which is implicated in producing

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

effects, and the serotonin 5-HT_2B receptor, which is implicated in causing cardiac valvulopathy. However, MDAI shows significant affinity for all three of the α₂-adrenergic receptors (K_i = 322 to 1121nM).

Effects

The family of drugs typified by

produce their effects through multiple mechanisms of action in the body, and consequently produce three distinct cues which animals can be trained to respond to: a stimulant cue typified by drugs such as

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

, a psychedelic cue typified by drugs such as

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

and DOM, and an "entactogen-like" cue which is produced by drugs such as MDAI and MBDB. These drugs cause drug-appropriate responses in animals trained to recognize the effects of MDMA, but do not produce responses in animals trained selectively to respond to stimulants or hallucinogens. Because these compounds selectively release serotonin in the brain but have little effect on dopamine or noradrenaline levels, they can produce empathogenic effects but without any stimulant action, instead being somewhat sedating. A 2024 study compared the effects of MDAI and MDMA in humans. It found that MDAI produced comparable and very similar subjective effects to those of MDMA. This included pleasurable drug effects, drug liking, stimulation, happiness, openness, trust, and closeness. In addition, it included sense of well-being, emotional excitation, and extroversion, but not general activity or concentration, a profile of effects described as similar to that of MDMA. Other effects included a blissful state, experience of unity, and changed meaning of percepts, also described as comparable to MDMA. The effects of MDAI were slightly greater than those of 75mg MDMA and slightly lower than those of 125mg MDMA. At the employed dose of 3.0mg/kg, with 125mg MDMA corresponding to 1.9mg/kg, it was estimated that MDAI had about 60% of MDMA's potency in producing comparable psychoactive effects (hence, roughly 200mg MDAI would be similar to 125mg MDMA). Aside from subject effects, MDAI also increased

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

levels, and

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

levels similarly to MDMA. Conversely, it did not increase

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

Neurotoxicity

MDAI shows substantially lower serotonergic neurotoxicity than

in animals and has been described as a "non-neurotoxic" analogue of MDMA. However, MDAI still shows weak serotonergic neurotoxicity both alone and particularly in

with

in animals. As such, MDAI does not appear to be a fully non-neurotoxic alternative to MDMA.

Toxicity

Very high doses can be fatal in rats with a 50% fatality rate for those subcutaneously injected with 28 mg/kg of MDAI. This is a result of the way serotonin release interferes with thermoregulation.

Pharmacokinetics

The duration of MDAI in humans appears to be similar to that of MDMA at 2 to 5hours or up to around 6hours.

Chemistry

The

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

of MDAI is indirectly derived from that of the illicit drug MDA, but the α-

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

of the

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...

amino In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

side chain has been bound back to the

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

nucleus to form an

indane Indane or indan is an organic compound with the formula C9H10. It is a colorless liquid hydrocarbon. It is a petrochemical, a bicyclic compound. It occurs at the level of about 0.1% in coal tar. It is usually produced by hydrogenation of inde ...

ring system, which changes its pharmacological properties substantially.

Analogues

* 5,6-methylenedioxy-N-methyl-2-aminoindane * 5-methoxy-2-aminoindane * 5-methoxy-6-methyl-2-aminoindane * 5-iodo-2-aminoindane * 2-aminoindane * N-methyl-2-aminoindane

Synthesis

MDAI can be produced from 3-(3,4-methylenedioxyphenyl)propionic acid which is converted to the acid chloride and then heated to produce 5,6-methylenedioxy-1-indanone. Treatment of the indanone with amyl nitrite in methanol with HCl afforded the hydroxyimino ketone. This is reduced to the 2-aminoindan following a modification of Nichols' earlier method from a paper discussing DOM analogues, using a Pd/C catalyst in glacial

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...

with catalytic H₂SO₄.

Society and culture

Legal Status

China

As of October 2015 MDAI is a controlled substance in

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

Denmark

MDAI is illegal in

Denmark Denmark is a Nordic countries, Nordic country in Northern Europe. It is the metropole and most populous constituent of the Kingdom of Denmark,, . also known as the Danish Realm, a constitutionally unitary state that includes the Autonomous a ...

as of September 2015.

Finland

Scheduled in the "government decree on psychoactive substances banned from the consumer market".

Switzerland

As of December 2011 MDAI is a controlled substance in

Switzerland Switzerland, officially the Swiss Confederation, is a landlocked country located in west-central Europe. It is bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. Switzerland ...

References

{{DEFAULTSORT:Methylenedioxy-2-aminoindane, 5, 6- Designer drugs Entactogens Euphoriants Methylenedioxyphenethylamines Monoaminergic neurotoxins Serotonin-norepinephrine releasing agents